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Background. We compared the performance of the Liver Transplant Risk Score (LTRS) with the survival outcomes following liver transplantation (SOFT), pretransplant SOFT (P-SOFT), Balance of Risk Score (BAR), donor-age and model for end-stage liver disease (D-MELD), and Organ Procurement and Transplantation Network Risk Prediction Score (ORPS) for the prediction of 90-d mortality, 1-y mortality, and 5-y survival after first-time liver transplantation (LT). Methods. A retrospective analysis of the Scientific Registry of Transplant Recipients was conducted using data collected between 2002 and 2021. Results. A total of 82 696 adult LT recipients with a median age of 56 y were included. The area under the curve for 90-d mortality were 0.61, 0.66, 0.65, 0.61, 0.58, and 0.56 for the LTRS, SOFT, P-SOFT, BAR, D-MELD, and ORPS, respectively (all pairwise comparisons: P < 0.05). The area under the curve for 1-y mortality were 0.60, 0.63, 0.62, 0.59, 0.60, 0.57, and 0.59 for the LTRS, SOFT, P-SOFT, BAR, D-MELD, and ORPS, respectively (all pairwise comparisons: P < 0.05). The c-statistics for 5-y survival were not statistically significant among the models. For 90-d mortality, 1-y mortality, and 5-y survival, the correlation coefficients between the LTRS and P-SOFT (the 2 models requiring only preoperative parameters) were 0.90. 0.91, and 0.81, respectively (P

ABSTRACT: A middle-aged man presented to the hospital with chief complaint of worsening chest pain and shortness of breath. He was found to have methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia, acute hypoxic respiratory failure secondary to MSSA pneumonia and septic emboli. The patient underwent a transesophageal echocardiogram which revealed a large, mobile tricuspid valve vegetation secondary to endocarditis. The patient was initially managed conservatively with intravenous antibiotics and supportive measures. However, his respiratory status worsened due to persistence of a large tricuspid valve vegetation which progressed to bilateral septic pulmonary emboli with peripheral cavitary lesions identified on follow-up CT of the chest. In order to debulk the large tricuspid vegetation, the patient successfully underwent endovascular mechanical aspiration of tricuspid valve vegetation utilizing the 20-Fr INARI curved Flowtriever (INARI Medical, CA) catheter. This case highlights a new, minimally invasive technique and device employed in treating native valve vegetations caused by endocarditis as an alternative approach to surgery.

Objective:. To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery. Background:. Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability. Methods:. We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109). Results:. Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2–7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30–1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24–1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61–2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24–3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33–1.95) were associated with readmission. Conclusions:. Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures.

Summary:. Charcot–Marie–Tooth (CMT) disease is the most prevalent inherited neuromuscular disorder. It commonly leads to various musculoskeletal deformities, profoundly impacting the quality of life. The present case report explores the often under-recognized body image dissatisfaction in CMT, highlighting the potential benefits of a multidisciplinary approach to enhance aesthetic satisfaction. We present a case of a 54-year-old woman with CMT, who experienced chronic facial asymmetry, significantly impairing her quality of life. Seeking cosmetic enhancement, she underwent two sessions of facial treatment using hyaluronic acid-based fillers. The first session focused on correcting right mandibular hypoplasia and other facial asymmetries, whereas the second session focused on enhancing perioral aesthetics. The treatment resulted in significant aesthetic improvements, as demonstrated by high ratings in both the Physician Global Aesthetic Improvement Scale and the Subject Global Aesthetic Improvement Scale. Besides, there was a marked reduction in lip corner asymmetry, the patient’s primary concern. The role of hyaluronic acid fillers in facial aesthetic enhancement is well established, and their application in the context of CMT is a promising under-investigated field, to our knowledge. This case study highlights the importance of considering body image in CMT patients and suggests that minimally invasive aesthetic procedures can be a valuable addition to the multidisciplinary care of patients with inherited neurological disorders. Despite being a single-case study, the significant improvement in the patient’s aesthetic satisfaction requires further research in this field.

Objective:. To assess the effects of the 2020 United States Public Health Service (PHS) “Increased Risk” Guidelines update. Background:. Donors labeled as “Increased Risk” for transmission of infectious diseases have been found to have decreased organ utilization rates despite no significant impact on recipient survival. Recently, the PHS provided an updated guideline focused on “Increased Risk” organ donors, which included the removal of the “Increased Risk” label and the elimination of the separate informed consent form, although the actual increased risk status of donors is still ultimately transmitted to transplant physicians. We sought to analyze the effect of this update on organ utilization rates. Methods:. This was a retrospective analysis of the Organ Procurement and Transplantation Network database which compared donor organ utilization in the 2 years before the June 2020 PHS Guideline update for increased-risk donor organs (June 2018–May 2020) versus the 2 years after the update (August 2020–July 2022). The organ utilization rate for each donor was determined by dividing the number of organs transplanted by the total number of organs available for procurement. Student t test and multivariable logistic regression models were used for analysis. Results:. There were 17,272 donors in the preupdate cohort and 17,922 donors in the postupdate cohort; of these, 4,977 (28.8%) and 3,893 (21.7%) donors were considered “Increased Risk”, respectively. There was a 2% decrease in overall organ utilization rates after the update, driven by a 3% decrease in liver utilization rates and a 2% decrease in lung utilization rates. After multivariable adjustment, donors in the postupdate cohort had 10% decreased odds of having all organs transplanted. Conclusions:. The 2020 PHS “Increased Risk” Donor Guideline update was not associated with an increase in organ utilization rates in the first 2 years after its implementation, despite a decrease in the proportion of donors considered to be at higher risk. Further efforts to educate the community on the safe usage of high-risk organs are needed and may increase organ utilization.

Background: Pruritus can be an intolerable symptom in patients with cancer. Type 2 inflammation, and specifically, the cytokines IL-4, IL-13, and IL-31, play major roles in the itching process. Dupilumab is an antibody against IL-4Rα, which is a common IL-4 and IL-13 receptor subunit. Blocking IL-4 and IL-13 activity reduces the synthesis of IL-31, the “itch cytokine,” and receptors for these 3 cytokines are expressed on itch nerves. Dupilumab is approved for treating moderate-to-severe atopic dermatitis, of which itching is a significant symptom. Objective: The objective of this case study was to present the initial evidence of the safety and efficacy of dupilumab as a treatment for intractable malignancy-associated pruritus in 3 patients, thereby providing a basis for further investigation in a larger cohort. Methods: As a proof of concept, we used dupilumab in our center to treat 3 patients with intractable malignancy-associated pruritus. The first patient was a 73-year-old male with a history of prostate cancer, the second patient was a 75-year-old female with cutaneous T-cell lymphoma, and the third patient was a 32-year-old male with metastatic melanoma. All 3 patients experienced debilitating itching, which started at some stage after the malignancy had been diagnosed. Moreover, none of the 3 patients showed clinical evidence of atopic dermatitis or other causes of itching (eg, uremia or liver failure), and none of the 3 patients responded to conventional treatments for pruritus. Results: Biweekly treatment with dupilumab led to an immediate improvement in itching, which subsided entirely after a few doses without any significant adverse effects. Conclusion: We propose that dupilumab is a safe and effective treatment for intractable malignancy-associated pruritus, and we are currently testing it in a large cohort.

Focal axillary artery stenosis or occlusion is a rare occurrence that is most commonly encountered after severe trauma involving the shoulder joint or proximal humerus. Other etiologies that can lead to axillary artery injury or pathology include different vasculitides, radiation arteritis, crutch-injury, and peripheral arterial disease. In this case report, a 70-year-old woman was referred for asymmetrically decreased right brachial artery systolic pressure and right-hand paresthesia with overhead abduction. Further evaluation with imaging revealed critical stenosis of the right axillary artery. The focal stenotic lesion was treated with drug-coated balloon angioplasty and stent placement leading to in-line flow and resolution of symptoms. Duplex exam 6 months post-treatment demonstrated a widely patent right axillary artery stent without stenosis. Biannual clinic visits up to 2 years post stent placement confirmed resolution of symptoms.

Background: The impact of adjunctive anti-inflammatory treatment on outcomes for patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs) is unknown. Methods: Using data from the International KD Registry in patients with ≥ medium CAA we evaluate associations of treatment with outcomes and major adverse cardiac events (MACE). Results: Medium or large CAA was present in 527 (32%) patients. All were treated with intravenous immunoglobulin (IVIG), 70% were male, and the median age was 1.3 years (interquartile range: 0.4-4.0 years). The most common acute therapies included single IVIG alone in 243 (46%), multiple IVIG in 100 (19%), multiple IVIG + corticosteroids in 75 (14%), and multiple IVIG + infliximab + corticosteroids in 44 (8%) patients. Patients who received therapy beyond single IVIG had a larger CA z-score at baseline (P < 0.001) and a higher rate of bilateral CAA (P < 0.001). Compared with IVIG alone, early adjunctive treatments (within 3 days of initial IVIG) were not associated with time to CAA regression or MACE, whereas later adjunctive therapy was associated with MACE and longer time to CAA regression. Patients receiving IVIG plus steroids vs IVIG alone had a trend towards shorter time to CAA regression and lower risk of MACE (P = 0.07). A larger CAA z-score at baseline was the strongest predictor of an increase in the CAA z-score over follow-up, lower likelihood of CAA regression, and higher risk of MACE. Conclusions: Persistence of CAA and MACE are more strongly associated with baseline severity CAA than with acute adjuvant anti-inflammatory therapy. Patients who received late adjunctive therapy are at higher risk for worse outcomes. Résumé: Contexte: L’incidence d’un traitement anti-inflammatoire d’appoint chez les patients atteints de la maladie de Kawasaki (MK) compliquée d’anévrismes coronariens est inconnue. Méthodologie: À partir de données provenant du registre international de la maladie de Kawasaki portant sur les patients ayant subi des anévrismes coronariens modérés ou importants, nous avons évalué l’incidence des différents traitements sur les résultats cliniques et les événements cardiovasculaires indésirables majeurs (ECIM). Résultats: Des anévrismes coronariens modérés ou importants ont été relevés chez 527 patients (32 %). Tous les patients recevaient des immunoglobulines administrées par voie intraveineuse (IgIV); 70 % d’entre eux étaient de sexe masculin, et leur âge médian était de 1,3 an (écart interquartile : de 0,4 an à 4,0 ans). Les traitements d’urgence les plus fréquents comprenaient un seul traitement par IgIV chez 243 patients (46 %), plusieurs traitements par IgIV chez 100 patients (19 %), une association de plusieurs traitements IgIV et de corticostéroïdes chez 75 patients (14 %) et une association de plusieurs traitements IgIV, de corticostéroïdes et d’infliximab chez 44 patients (8 %). Les patients ayant reçu un traitement autre qu’un seul traitement IgIV présentaient des scores z initiaux plus élevés pour le diamètre des artères coronaires (P < 0,001) et un taux plus élevé d’anévrismes coronariens bilatéraux (P < 0,001). En comparaison d’un traitement par IgIV seulement, les traitements d’appoint précoces (administrés dans les trois jours suivant le début du traitement par IgIV) n’ont pas eu d’incidence sur la durée avant la régression des anévrismes coronariens ni sur la survenue d’ECIM, alors que les traitements d’appoint plus tardifs ont été associés à un risque plus élevé d’ECIM et à une régression plus tardive des anévrismes coronariens. Les patients ayant reçu une association d’IgIV et de corticostéroïdes avaient tendance à présenter une régression plus rapide des anévrismes coronariens et un plus faible risque d’ECIM que ceux recevant uniquement un traitement par IgIV (P = 0,07). Un score z initial plus élevé pour un anévrisme coronarien était le facteur prédictif le plus puissant d’une augmentation du score z pendant la période de suivi, d’une probabilité plus faible de régression de l’anévrisme et d’un risque plus élevé d’ECIM. Conclusions: La gravité initiale de l’anévrisme coronarien est plus fortement associée à la persistance de l’anévrisme et à la survenue d’ECIM que le recours à un traitement anti-inflammatoire d’urgence en appoint. Les patients recevant un traitement d’appoint tardif étaient par ailleurs plus susceptibles de présenter des résultats défavorables.

Background:. Hyaluronic acid filler injections are regarded as the gold standard procedure for facial rejuvenation. Standing as the second most injected cosmetic filler, calcium hydroxyapatite-based fillers are also widely used worldwide. However, to our knowledge, prospective studies assessing patient satisfaction and sonographic changes in dermal thickness after a single session of a hybrid filler combining hyaluronic acid and calcium hydroxyapatite have not been previously published. Methods:. This was a single-center, prospective, quasi-experimental study comprising 15 participants between 32 and 63 years of age. Each participant received a single-session treatment based on facial subcutaneous injections of HArmonyCa, a hybrid combination filler comprising hyaluronic acid and calcium hydroxyapatite. This study involved an intrapatient control design and a 120-day follow-up with clinical and sonographic assessment. For this purpose, standardized photographic images, high-frequency ultrasound evaluations, and physician- and patient-oriented overall aesthetic improvement scores were recorded at 0, 30, 90, and 120 following the procedure. Results:. According to our findings, 20% of the subjects had an exceptional improvement; 20%, “very improved”; and 60%, “improved.” Intrapatient sonographic comparison showed a significant increase in dermal thickness, at 90 and 120 days, only on the side treated (P < 0.001). Conclusion:. In our clinical study, a single-session treatment with a hybrid product combining hyaluronic acid and calcium hydroxyapatite resulted in positive cosmetic satisfaction and increased dermal thickness.

The dynamics of heavy metal concentrations in the sediments of mangroves are crucial for understanding the health and sustainability of these ecosystems. This study, conducted in a conservation area of Ujung Kulon National Park (UKNP) in Indonesia, investigated the distribution of heavy metals in mangrove sediments, which are vital in trapping these potentially harmful substances due to their absorption, sedimentation, and bioaccumulation capabilities. By analyzing sediment cores from different intertidal zones (interior, fringe, and mudflat) through Inductively Coupled Plasma - Optical Emission Spectrometry (ICP-OES), this study examined concentrations and distribution patterns of six heavy metals: manganese (Mn), copper (Cu), zinc (Zn), cobalt (Co), chromium (Cr), and Iron (Fe). The results indicated that the average concentration of heavy metals followed a decreasing order of Fe> Mn > Zn > Cu > Cr> Co across all locations. All of the heavy metals in the interior and fringe increased gradually from the year 1900 to the present; on the contrary, the mudflat decreased over the same period. Enrichment Factor (EF) and Geo Accumulation Index (Igeo) were used to evaluate heavy metal pollution levels comprehensively. The study revealed temporal trends in heavy metal concentrations, highlighting the need for further research to mitigate these contaminant's effects on mangrove ecosystems. By integrating the EF, the Igeo index, and quality standards, the research demonstrates that UKNP is likely pristine. Furthermore, this work emphasizes the need to utilize dated environmental archives to reconstruct historical patterns in trace metal pollution in locations where long-term environmental studies remain particularly limited. [ABSTRACT FROM AUTHOR]

Background: Since April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. Conclusions: There is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies. Résumé: Contexte: Depuis avril 2020, de nombreux cas d’enfants présentant une inflammation généralisée, se trouvant souvent dans un état critique et montrant des signes d’une infection récente au coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), ont été signalés. On pense que cet état, désigné depuis sous le nom de syndrome inflammatoire multisystémique de l’enfant (SIME), pourrait être une réponse immunitaire tardive au virus de la maladie à coronavirus 2019 (COVID-19); les patients présentent souvent des manifestations cardiaques associées à une dysfonction ventriculaire ou à une dilatation des artères coronaires. Méthodologie: Nous avons mené un sondage sur les stratégies de prise en charge du SIME en milieu hospitalier auprès des membres du registre international de la maladie de Kawasaki, qui sont rattachés à 38 établissements répartis dans 11 pays. Résultats: Au total, 56 % des répondants ont déclaré opter pour un traitement immunomodulateur pour tous les patients présentant un SIME, quelles qu’en soient les manifestations. Tous les répondants ont déclaré avoir recours à l’administration d’immunoglobulines par voie intraveineuse, 53 % d’entre eux utilisant ce traitement chez tous les patients. Les stéroïdes étaient plus souvent utilisés chez les patients présentant des symptômes cliniques graves ou ne répondant pas aux immunoglobulines administrées par voie intraveineuse; seule une minorité de répondants ont déclaré utiliser des stéroïdes chez tous les patients (14 %). Les répondants utilisaient aussi fréquemment l’acide acétylsalicylique (91 %), à des doses anti-inflammatoires ou antiplaquettaires. Ils ont en outre déclaré avoir recours à des anticoagulants en prophylaxie, en particulier chez les patients présentant un risque élevé de thromboembolie veineuse, et à une anticoagulothérapie chez les patients présentant des anévrismes coronaires géants. Conclusions: La prise en charge des patients présentant un SIME varie d’un médecin à l’autre, et les données permettant d’évaluer la supériorité des divers traitements employés sont insuffisantes; il conviendrait donc de mettre en place des initiatives de collaboration afin de combler les lacunes des connaissances et d’optimiser les stratégies thérapeutiques.

Objective: To investigate the association between using febuxostat and cardiovascular events. Methods: Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality. Results: A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; I2=48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; I2 =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; I2=26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; I2 =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; I2=0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; I2=58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease. Conclusion: This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.

Here, we prepared two kinds of nanocomposites (MCT#1 and MCT#2) involving MWCNTs and TiO2 nanoparticles. The characterisation of the samples is carried out based on FTIR spectroscopy and TEM. The Ti-O groups that is attributed to the TiO2 nanoparticles can be confirmed according to the FTIR analysis. TEM images show that the average particle size of TiO2 nanoparticles in prepare MCT#1 and MCT#2 is equal to 13 nm and 15 nm, respectively. The influences of nanocomposites weight fraction and illumination time are investigated on the decomposition rate of methyl orange (MO) as pollutant. The photocatalytic results exhibit that the decomposition rate of MO is increased with respect to the weight fraction and illumination time. Meanwhile, higher decomposition rate can be observed using MCT#2 compared to MCT#1. Statistical analysis of the results based on Duncan's multiple range test at α = 0.05 reveals that all of the applied levels of the factors have a significant effect on the decomposition rate. The response surface results confirm that the effect of illumination time is high that that of weight fraction of MCT#1 and MCT#2. [ABSTRACT FROM AUTHOR]

Background. Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients >65. Methods. We conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites. Results. One thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were >65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival. Conclusions. By targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients.

Antithyroid drug-induced severe liver injury is an uncommon but serious complication. We hereby delineate the case of a 38-year-old female who presented to the emergency department for an impending thyroid storm. After initiation of a single dose of propylthiouracil, her liver enzymes went into the thousands. She was subsequently admitted to the intensive care unit. Propylthiouracil was discontinued and corticosteroids were initiated with the resolution of her elevated liver enzymes. On follow-up, her liver function was at its baseline and thyroid hormone levels were under control. We hope this report will encourage clinicians to cast a broad differential diagnosis in patients presenting with liver injury in the acute setting. Furthermore, it is imperative to raise awareness regarding the ever-increasing list of pharmacologic agents that can perpetuate drug-induced hepatotoxicity.